Ion channels are transmembrane multi-subunit proteins embedded in the cellular plasma membranes of living cells which permit the passage of specific ions from the extracellular side of the plasma membrane to the intracellular region of the cell. Specific ion transport is facilitated by a central aqueous pore which is capable of opening and closing due to changes in pore conformation. When the ion gate is open, ions flow freely through the channel. When the ion gate is closed, ions are prevented from permeating the channel. Ion channels are found in a multitude of multicellular eukaryotic species and in a myriad of different cell types. Ion channels may be either voltage-gated or ligand-gated. Channel gating is the process by which a particular channel is either open or closed. An ion channel may be capable of occupying a range of different “open” or “closed” states. The gating process may therefore require a particular sequence of transition states or inclusion of alternative transition states before a channel attains a particular level of gating. The gating process is modulated by a substance or agent, which in some way alters or affects the manner in which the channel opens or closes. A channel may be gated by a ligand such as a neurotransmitter, an internal primary or secondary messenger, or other bioactive agent. The ligand either attaches to one or more binding sites on the channel protein or attaches to a receptor that is associated with the channel. If the channel is voltage-gated, changes in the membrane potential trigger channel gating by conformational changes of charged elements within the channel protein. Whether a channel is ligand-gated or voltage-gated, a change in one part of the channel produces an effect in a different part of the channel which results in the opening or closing of a permeant pathway.
Transient receptor potential (TRP) proteins are a diverse family of proteins with structural features typical of ion channels. TRP proteins are expressed in a verity of organisms, tissues, and cell types, including electrically excitable and nonexcitable cells. The TRP channels have been divided into three main subfamilies: TRPC for “canonical”, TRPM for “melastinin-like”, and TRPV for “vanilloid-receptor-like”.5 All TRP channels discovered thus far are composed of six putative transmembrane domains and a slightly hydrophobic pore-forming region. Both the N- and C-terminal domains of the TRP proteins are intracytoplasmic. Despite these similarities of structure, the functions of TRP channels are different from one channel to another, even amongst the members of the same subfamily.
The human TPRM subfamily currently consists of eight members. The activation mechanisms of several TPRM proteins have been elucidated and each has been shown to have specific ion selectivity and a particular mechanism of action.